Nucleophile-reactive sulfonated compounds for the (radio)labelling of (bio) molecules; precursors and conjugates thereof

Abstract

Nucleophile-reactive sulfonated compounds used as precursors to (radio)labelled (bio)molecules are produced by pre-introduction of a nucleophilic compound R* through an unusual nucleophile-induced ring-opening reaction of the sultone moiety of the precursor. The precursors and compounds conform to respective formulae (Ip) and (I): Also disclosed are methods for producing these precursors and compounds, as well as for conjugation of these compounds with (bio)molecules, and to the drugs obtained by this method.

The invention claimed is: 
     
       1. A precursor compound, the formula of which is: 
       
         
           
           
               
               
           
         
       
       wherein
 R 0  is a spacer selected from the group consisting of the following radicals: 
 
       
         
           
           
               
               
           
         
         R 2′ corresponds to hydrogen, an alkyl, a cyclo-alkyl, an aryl, an arylalkyl, an alkylaryl, an acyl, an alkenyl, an alkynyl radical or a combination of these radicals; 
         R 3  corresponds to a hydrocarbon moiety; 
         R 10  is a protective monovalent group that avoids any side reaction on the carboxylic function and corresponds to an alkyl, a cyclo-alkyl or a hydrogen or selected among radicals R 1 , wherein R 1  is an activating group of the oxygen atom of the ester function; 
         the functional units of formula COOR 10  and 
       
       
         
           
           
               
               
           
         
         being nucleophile-reactive, the nucleophilic reactivity of these functional units being different, COOR 10 's nucleophilic reactivity being less than the nucleophilic reactivity of 
       
       
         
           
           
               
               
           
         
       
     
     
       2. A precursor compound according to  claim 1  of the formula (IIp): 
       
         
           
           
               
               
           
         
       
       wherein
 R 10  is a protective monovalent group that avoids any side reaction on the carboxylic function and corresponds to an alkyl, a cyclo-alkyl, or a hydrogen or selected among radicals R 1 , wherein R 1  is an activating group of the oxygen atom of the ester function; 
 the functional units of formula COOR 10  and 
 
       
         
           
           
               
               
           
         
         being nucleophile-reactive, the nucleophilic reactivity of these functional units being different, COOR 10 's nucleophilic reactivity being less than the nucleophilic reactivity of 
       
       
         
           
           
               
               
           
         
       
     
     
       3. The compound of  claim 1 , wherein R 3  is a radical —(CR 4 R 5 ) n —, wherein R 4 , R 5  represents individually hydrogen or an alkyl, a cyclo-alkyl, an aryl, an arylalkyl, an alkylaryl, an acyl, an alkenyl, an alkynyl radical or a combination of these radicals; and n is an integer between 1 and 3. 
     
     
       4. The compound of  claim 3 , wherein R 4  and R 5  represent hydrogen.